Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane proteins.
Cell Line
Cell Line, Tumor
Cytosol
/ metabolism
Deubiquitinating Enzymes
/ metabolism
Endoplasmic Reticulum
/ metabolism
HEK293 Cells
HeLa Cells
Humans
Hydrophobic and Hydrophilic Interactions
Membrane Proteins
/ metabolism
Protein Domains
/ physiology
Protein Transport
/ physiology
Ubiquitin
/ metabolism
Ubiquitin Thiolesterase
/ metabolism
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
03 05 2021
03 05 2021
Historique:
received:
12
04
2020
revised:
19
12
2020
accepted:
24
02
2021
entrez:
1
4
2021
pubmed:
2
4
2021
medline:
29
9
2021
Statut:
ppublish
Résumé
Numerous proteins that have hydrophobic transmembrane domains (TMDs) traverse the cytosol and posttranslationally insert into cellular membranes. It is unclear how these hydrophobic membrane proteins evade recognition by the cytosolic protein quality control (PQC), which typically recognizes exposed hydrophobicity in misfolded proteins and marks them for proteasomal degradation by adding ubiquitin chains. Here, we find that tail-anchored (TA) proteins, a vital class of membrane proteins, are recognized by cytosolic PQC and are ubiquitinated as soon as they are synthesized in cells. Surprisingly, the ubiquitinated TA proteins are not routed for proteasomal degradation but instead are handed over to the targeting factor, TRC40, and delivered to the ER for insertion. The ER-associated deubiquitinases, USP20 and USP33, remove ubiquitin chains from TA proteins after their insertion into the ER. Thus, our data suggest that deubiquitinases rescue posttranslationally targeted membrane proteins that are inappropriately ubiquitinated by PQC in the cytosol.
Identifiants
pubmed: 33792613
pii: 211933
doi: 10.1083/jcb.202004086
pmc: PMC8020466
pii:
doi:
Substances chimiques
Membrane Proteins
0
USP20 protein, human
0
Ubiquitin
0
Deubiquitinating Enzymes
EC 3.4.19.12
USP33 protein, human
EC 3.4.19.12
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM117386
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG056800
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007223
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 Culver and Mariappan.
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